These studies involve the generation, characterization, and utilization of monoclonal antibodies (MAbs) directed against antigens associated with human carcinomas. These MAbs are being used to better understand the cell biology and pathogenesis of several human carcinomas and to provide reagents that may be useful in several areas of the management of human carcinoma. These include in vitro diagnosis via serum assays and/or immunohistopathology, in vivo diagnosis such as gamma scanning, and potentially therapy. The MAbs generated can be classified into two groups based on the expression of the detected antigens. These are (a) antigens differentially expressed in human carcinoma versus normal adult tissues, such as the pancarcinoma tumor-associated glycoprotein (TAG)-72 which is detected by MAbs B72.3 and CC49, and carcinoembryonic antigen (CEA) which is detected by MAbs COL-1 through COL-1 5; or (b) tissue-associated antigens, such as the colon-associated antigen detected by MAb D612. Since MAb B72.3 has been shown to selectively target a range of carcinomas in clinical trials involving over 1000 patients, studies were conducted to characterize a series of 'second generation' MAbs to the TAG-72 antigen. These studies demonstrated that some of these second generation CC MAbs, such as CC83 and CC49, have a higher affinity constant for TAG-72 than B72.3, and may be better suited than B72.3 for some clinical applications. The presence of TAG-72 in serum samples from 260 patients with colorectal disease (malignant or benign) has been evaluated using the CA72-4 assay. Approximately 40% of patients with colorectal cancer exhibit elevated levels of this marker, moreover, the presence of positive levels of TAG-72 significantly correlates with advanced stages of disease. These studies suggest that the simultaneous use of TAG-72 and CEA serum markers may be useful in the diagnosis of recurrent disease and may therefore play a role in the clinical management of cancer patients.